KPNA2 is a promising biomarker candidate for esophageal squamous cell carcinoma and correlates with cell proliferation

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignant cancers worldwide, with a poor 5-year prognosis. Karyopherin α 2 (KPNA2) is a nuclear membrane protein that mediates nucleus-to-cytoplasm shuttling. Its expression is elevated in multiple forms of cancer, and it can be secreted into the serum. However, the concentration of KPNA2 in serum from ESCC patients and the role of KPNA2 in ESCC cells remains unclear. The aim of the present study was to determine the concentration of KPNA2 in serum from ESCC patients and to investigate the effect of KPNA2 silencing on ESCC cell proliferation. KPNA2 protein expression was detected at the tissue level by immunohistochemistry, in cell lines by western blotting and at the serum level by enzyme linked immunosorbent assay (ELISA). Cell proliferation was determined by cell growth curve and colony formation assay. Stages of the cell cycle were analyzed by flow cytometry. The effect of KPNA2 knockdown on E2F1 translocation was determined by subcellular fractionation. KPNA2 was overexpressed in both ESCC tissues and cell lines compared with controls. The concentration of KPNA2 in serum from ESCC patients was significantly higher than that from healthy controls. The AUC was determined to be 0.804. The sensitivity and specificity of the assay were 76.7 and 75.0%, respectively. To determine the significance of KPNA2 function, small interfering RNA (siRNA) against KPNA2 was used to knock down KPNA2 levels in the ESCC using siRNA in the Kyse510 cell line. KPNA2 siRNA inhibited Kyse510 cell proliferation and colony formation ability and induced a G2/M phase arrest. The nuclear translocation of E2F1 was also reduced in siRNA-treated Kyse510 cells. The KPNA2 protein levels were high in ESCC tumors, and siRNA against KPNA2 could inhibit the growth of ESCC cells, suggesting it may be a new potent marker and therapeutic target for ESCC.

Prognostic value of increased KPNA2 expression in some solid tumors: A systematic review and meta-analysis

“…Existing evidences have shown that KPNA2 was over-expressed in multiple malignancies [9–11]. Meanwhile, it has been suggest that elevated KPNA2 could be associated with poor prognosis in a variety of solid tumors, including colorectal cancer [11–13], breast cancer [14–17], gastric cancer [10, 18, 19] and hepatocellular carcinoma [20, 21].…”

KPNA2 Contributes to the Inflammatory Processes in Synovial Tissue of Patients with Rheumatoid Arthritis and SW982 Cells

“…Karyopherin-α2 (KPNA2), a member of the importin family, is a kind of nuclear transport proteins [8]. One of the last major steps of the most intracellular signaling pathways is nucleocytoplasmic transport [9].…”

Association of overexpressed karyopherin alpha 2 with poor survival and its contribution to interleukin‐1β‐induced matrix metalloproteinase expression in oral cancer

“…Karyopherin alpha 2 (KPNA2), which also known as importin α1, belongs to the karyopherin family; it delivers numerous cargo proteins to the nucleus and is then translocated back into the cytoplasmic compartments in a Ran‐GTP‐dependent manner . Aberrant KPNA2 expression has been observed in various human cancers, including lung cancer, breast cancer, melanoma, cervical cancer, esophageal SCC, ovarian cancer, prostate cancer, liver cancer, bladder cancer, brain cancer, gastric cancer, upper tract urothelial carcinoma, cholangiocarcinoma, and colorectal cancer . The KPNA2 overexpression is associated with tumor invasiveness and a poor prognosis in several malignancies .…”

“…The KPNA2 overexpression is associated with tumor invasiveness and a poor prognosis in several malignancies . Notably, it has been shown that KPNA2 can be secreted by cancer cells, and higher KPNA2 levels have been detected in the serum samples of patients with lung, ovarian, and colorectal cancer compared with those in healthy controls . However, the clinical and biological significance of KPNA2 in oral cavity SCC has not been clarified.…”

“…10 Aberrant KPNA2 expression has been observed in various human cancers, including lung cancer, breast cancer, melanoma, cervical cancer, esophageal SCC, ovarian cancer, prostate cancer, liver cancer, bladder cancer, brain cancer, gastric cancer, upper tract urothelial carcinoma, cholangiocarcinoma, and colorectal cancer. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] The KPNA2 overexpression is associated with tumor invasiveness and a poor prognosis in several malignancies. [16][17][18][19]25,27,28 Notably, it has been shown that KPNA2 can be secreted by cancer cells, 14 and higher KPNA2 levels have been detected in the serum samples of patients with lung, ovarian, and colorectal cancer compared with those in healthy controls.…”